Phosphorylation of parkin by Parkinson disease-linked kinase PINK1 activates parkin E3 ligase function and NF-B signaling
Identifieur interne : 001D63 ( Main/Corpus ); précédent : 001D62; suivant : 001D64Phosphorylation of parkin by Parkinson disease-linked kinase PINK1 activates parkin E3 ligase function and NF-B signaling
Auteurs : Di Sha ; Lih-Shen Chin ; Lian LiSource :
- Human Molecular Genetics [ 0964-6906 ] ; 2010-01-15.
Abstract
Mutations in PTEN-induced putative kinase 1 (PINK1) or parkin cause autosomal recessive forms of Parkinson disease (PD), but how these mutations trigger neurodegeneration is poorly understood and the exact functional relationship between PINK1 and parkin remains unclear. Here, we report that PINK1 regulates the E3 ubiquitin-protein ligase function of parkin through direct phosphorylation. We find that phosphorylation of parkin by PINK1 activates parkin E3 ligase function for catalyzing K63-linked polyubiquitination and enhances parkin-mediated ubiquitin signaling through the IB kinase/nuclear factor B (NF-B) pathway. Furthermore, the ability of PINK1 to promote parkin phosphorylation and activate parkin-mediated ubiquitin signaling is impaired by PD-linked pathogenic PINK1 mutations. Our findings support a direct link between PINK1-mediated phosphorylation and parkin-mediated ubiquitin signaling and implicate the deregulation of the PINK1/parkin/NF-B neuroprotective signaling pathway in the pathogenesis of PD.
Url:
DOI: 10.1093/hmg/ddp501
Links to Exploration step
ISTEX:BBE18E16E039361A51A15C00DB20B747444E29B7Le document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title>Phosphorylation of parkin by Parkinson disease-linked kinase PINK1 activates parkin E3 ligase function and NF-B signaling</title><author><name sortKey="Sha, Di" sort="Sha, Di" uniqKey="Sha D" first="Di" last="Sha">Di Sha</name><affiliation><mods:affiliation>Department of Pharmacology and Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, GA 30322, USA</mods:affiliation></affiliation></author><author><name sortKey="Chin, Lih Shen" sort="Chin, Lih Shen" uniqKey="Chin L" first="Lih-Shen" last="Chin">Lih-Shen Chin</name><affiliation><mods:affiliation>E-mail: chinl@pharm.emory.edu</mods:affiliation></affiliation></author><author><name sortKey="Li, Lian" sort="Li, Lian" uniqKey="Li L" first="Lian" last="Li">Lian Li</name><affiliation><mods:affiliation>E-mail: chinl@pharm.emory.edu</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:BBE18E16E039361A51A15C00DB20B747444E29B7</idno><date when="2010" year="2010">2010</date><idno type="doi">10.1093/hmg/ddp501</idno><idno type="url">https://api.istex.fr/document/BBE18E16E039361A51A15C00DB20B747444E29B7/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">001D63</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a">Phosphorylation of parkin by Parkinson disease-linked kinase PINK1 activates parkin E3 ligase function and NF-B signaling</title><author><name sortKey="Sha, Di" sort="Sha, Di" uniqKey="Sha D" first="Di" last="Sha">Di Sha</name><affiliation><mods:affiliation>Department of Pharmacology and Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, GA 30322, USA</mods:affiliation></affiliation></author><author><name sortKey="Chin, Lih Shen" sort="Chin, Lih Shen" uniqKey="Chin L" first="Lih-Shen" last="Chin">Lih-Shen Chin</name><affiliation><mods:affiliation>E-mail: chinl@pharm.emory.edu</mods:affiliation></affiliation></author><author><name sortKey="Li, Lian" sort="Li, Lian" uniqKey="Li L" first="Lian" last="Li">Lian Li</name><affiliation><mods:affiliation>E-mail: chinl@pharm.emory.edu</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Human Molecular Genetics</title><idno type="ISSN">0964-6906</idno><idno type="eISSN">1460-2083</idno><imprint><publisher>Oxford University Press</publisher><date type="published" when="2010-01-15">2010-01-15</date><biblScope unit="volume">19</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="352">352</biblScope><biblScope unit="page" to="363">363</biblScope></imprint><idno type="ISSN">0964-6906</idno></series><idno type="istex">BBE18E16E039361A51A15C00DB20B747444E29B7</idno><idno type="DOI">10.1093/hmg/ddp501</idno><idno type="ArticleID">ddp501</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0964-6906</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract">Mutations in PTEN-induced putative kinase 1 (PINK1) or parkin cause autosomal recessive forms of Parkinson disease (PD), but how these mutations trigger neurodegeneration is poorly understood and the exact functional relationship between PINK1 and parkin remains unclear. Here, we report that PINK1 regulates the E3 ubiquitin-protein ligase function of parkin through direct phosphorylation. We find that phosphorylation of parkin by PINK1 activates parkin E3 ligase function for catalyzing K63-linked polyubiquitination and enhances parkin-mediated ubiquitin signaling through the IB kinase/nuclear factor B (NF-B) pathway. Furthermore, the ability of PINK1 to promote parkin phosphorylation and activate parkin-mediated ubiquitin signaling is impaired by PD-linked pathogenic PINK1 mutations. Our findings support a direct link between PINK1-mediated phosphorylation and parkin-mediated ubiquitin signaling and implicate the deregulation of the PINK1/parkin/NF-B neuroprotective signaling pathway in the pathogenesis of PD.</div></front></TEI><istex><corpusName>oup</corpusName><author><json:item><name>Di Sha</name><affiliations><json:string>Department of Pharmacology and Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, GA 30322, USA</json:string></affiliations></json:item><json:item><name>Lih-Shen Chin</name><affiliations><json:string>E-mail: chinl@pharm.emory.edu</json:string></affiliations></json:item><json:item><name>Lian Li</name><affiliations><json:string>E-mail: chinl@pharm.emory.edu</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>ARTICLES</value></json:item></subject><language><json:string>eng</json:string></language><abstract>Mutations in PTEN-induced putative kinase 1 (PINK1) or parkin cause autosomal recessive forms of Parkinson disease (PD), but how these mutations trigger neurodegeneration is poorly understood and the exact functional relationship between PINK1 and parkin remains unclear. Here, we report that PINK1 regulates the E3 ubiquitin-protein ligase function of parkin through direct phosphorylation. We find that phosphorylation of parkin by PINK1 activates parkin E3 ligase function for catalyzing K63-linked polyubiquitination and enhances parkin-mediated ubiquitin signaling through the IB kinase/nuclear factor B (NF-B) pathway. Furthermore, the ability of PINK1 to promote parkin phosphorylation and activate parkin-mediated ubiquitin signaling is impaired by PD-linked pathogenic PINK1 mutations. Our findings support a direct link between PINK1-mediated phosphorylation and parkin-mediated ubiquitin signaling and implicate the deregulation of the PINK1/parkin/NF-B neuroprotective signaling pathway in the pathogenesis of PD.</abstract><qualityIndicators><score>7.584</score><pdfVersion>1.5</pdfVersion><pdfPageSize>612 x 797.953 pts</pdfPageSize><refBibsNative>false</refBibsNative><keywordCount>1</keywordCount><abstractCharCount>1025</abstractCharCount><pdfWordCount>7176</pdfWordCount><pdfCharCount>48023</pdfCharCount><pdfPageCount>12</pdfPageCount><abstractWordCount>132</abstractWordCount></qualityIndicators><title>Phosphorylation of parkin by Parkinson disease-linked kinase PINK1 activates parkin E3 ligase function and NF-B signaling</title><genre><json:string>research-article</json:string></genre><host><volume>19</volume><pages><last>363</last><first>352</first></pages><issn><json:string>0964-6906</json:string></issn><issue>2</issue><genre></genre><language><json:string>unknown</json:string></language><eissn><json:string>1460-2083</json:string></eissn><title>Human Molecular Genetics</title></host><categories><wos><json:string>BIOCHEMISTRY & MOLECULAR BIOLOGY</json:string><json:string>GENETICS & HEREDITY</json:string></wos></categories><publicationDate>2010</publicationDate><copyrightDate>2010</copyrightDate><doi><json:string>10.1093/hmg/ddp501</json:string></doi><id>BBE18E16E039361A51A15C00DB20B747444E29B7</id><fulltext><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/BBE18E16E039361A51A15C00DB20B747444E29B7/fulltext/pdf</uri></json:item><json:item><original>false</original><mimetype>application/zip</mimetype><extension>zip</extension><uri>https://api.istex.fr/document/BBE18E16E039361A51A15C00DB20B747444E29B7/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/BBE18E16E039361A51A15C00DB20B747444E29B7/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a">Phosphorylation of parkin by Parkinson disease-linked kinase PINK1 activates parkin E3 ligase function and NF-B signaling</title><respStmt xml:id="ISTEX-API" resp="Références bibliographiques récupérées via GROBID" name="ISTEX-API (INIST-CNRS)"></respStmt></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Oxford University Press</publisher><availability><p>OUP</p></availability><date>2009-11-11</date></publicationStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a">Phosphorylation of parkin by Parkinson disease-linked kinase PINK1 activates parkin E3 ligase function and NF-B signaling</title><author><persName><forename type="first">Di</forename><surname>Sha</surname></persName><affiliation>Department of Pharmacology and Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, GA 30322, USA</affiliation></author><author><persName><forename type="first">Lih-Shen</forename><surname>Chin</surname></persName><email>chinl@pharm.emory.edu</email></author><author><persName><forename type="first">Lian</forename><surname>Li</surname></persName><email>chinl@pharm.emory.edu</email></author></analytic><monogr><title level="j">Human Molecular Genetics</title><idno type="pISSN">0964-6906</idno><idno type="eISSN">1460-2083</idno><imprint><publisher>Oxford University Press</publisher><date type="published" when="2010-01-15"></date><biblScope unit="volume">19</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="352">352</biblScope><biblScope unit="page" to="363">363</biblScope></imprint></monogr><idno type="istex">BBE18E16E039361A51A15C00DB20B747444E29B7</idno><idno type="DOI">10.1093/hmg/ddp501</idno><idno type="ArticleID">ddp501</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2009-11-11</date></creation><langUsage><language ident="en">en</language></langUsage><abstract><p>Mutations in PTEN-induced putative kinase 1 (PINK1) or parkin cause autosomal recessive forms of Parkinson disease (PD), but how these mutations trigger neurodegeneration is poorly understood and the exact functional relationship between PINK1 and parkin remains unclear. Here, we report that PINK1 regulates the E3 ubiquitin-protein ligase function of parkin through direct phosphorylation. We find that phosphorylation of parkin by PINK1 activates parkin E3 ligase function for catalyzing K63-linked polyubiquitination and enhances parkin-mediated ubiquitin signaling through the IB kinase/nuclear factor B (NF-B) pathway. Furthermore, the ability of PINK1 to promote parkin phosphorylation and activate parkin-mediated ubiquitin signaling is impaired by PD-linked pathogenic PINK1 mutations. Our findings support a direct link between PINK1-mediated phosphorylation and parkin-mediated ubiquitin signaling and implicate the deregulation of the PINK1/parkin/NF-B neuroprotective signaling pathway in the pathogenesis of PD.</p></abstract></profileDesc><revisionDesc><change when="2009-11-11">Created</change><change when="2010-01-15">Published</change><change xml:id="refBibs-istex" who="#ISTEX-API" when="2016-3-15">References added</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/BBE18E16E039361A51A15C00DB20B747444E29B7/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="corpus oup" wicri:toSee="no header"><istex:xmlDeclaration>version="1.0" encoding="utf-8"</istex:xmlDeclaration><istex:docType PUBLIC="-//NLM//DTD Journal Publishing DTD v2.3 20070202//EN" URI="journalpublishing.dtd" name="istex:docType"></istex:docType><istex:document><article article-type="research-article"><front><journal-meta><journal-id journal-id-type="publisher-id">hmg</journal-id><journal-id journal-id-type="hwp">hmg</journal-id><journal-title>Human Molecular Genetics</journal-title><issn pub-type="ppub">0964-6906</issn><issn pub-type="epub">1460-2083</issn><publisher><publisher-name>Oxford University Press</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.1093/hmg/ddp501</article-id><article-id pub-id-type="publisher-id">ddp501</article-id><article-categories><subj-group subj-group-type="heading"><subject>ARTICLES</subject></subj-group></article-categories><title-group><article-title>Phosphorylation of parkin by Parkinson disease-linked kinase PINK1 activates parkin E3 ligase function and NF-&kgr;B signaling</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Sha</surname><given-names>Di</given-names></name></contrib><contrib contrib-type="author"><name><surname>Chin</surname><given-names>Lih-Shen</given-names></name><xref ref-type="corresp" rid="cor1">*</xref></contrib><contrib contrib-type="author"><name><surname>Li</surname><given-names>Lian</given-names></name><xref ref-type="corresp" rid="cor1">*</xref></contrib></contrib-group><aff><addr-line>Department of Pharmacology and Center for Neurodegenerative Disease</addr-line>, <institution>Emory University School of Medicine</institution>, <addr-line>Atlanta, GA 30322</addr-line>, <country>USA</country></aff><author-notes><corresp id="cor1"><label>*</label>To whom correspondence should be addressed. Tel: <phone>+1 4047270361</phone>; Fax: <fax>+1 4047270365</fax>; Email: <email>chinl@pharm.emory.edu</email>/<email>lianli@pharm.emory.edu</email></corresp></author-notes><pub-date pub-type="ppub"><day>15</day><month>1</month><year>2010</year></pub-date><pub-date pub-type="epub"><day>11</day><month>11</month><year>2009</year></pub-date><volume>19</volume><issue>2</issue><fpage>352</fpage><lpage>363</lpage><history><date date-type="received"><day>16</day><month>8</month><year>2009</year></date><date date-type="accepted"><day>28</day><month>10</month><year>2009</year></date></history><copyright-statement>© The Author 2009. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org</copyright-statement><copyright-year>2010</copyright-year><abstract><p>Mutations in <italic>PTEN-induced putative kinase 1 (PINK1)</italic> or <italic>parkin</italic> cause autosomal recessive forms of Parkinson disease (PD), but how these mutations trigger neurodegeneration is poorly understood and the exact functional relationship between PINK1 and parkin remains unclear. Here, we report that PINK1 regulates the E3 ubiquitin-protein ligase function of parkin through direct phosphorylation. We find that phosphorylation of parkin by PINK1 activates parkin E3 ligase function for catalyzing K63-linked polyubiquitination and enhances parkin-mediated ubiquitin signaling through the I&kgr;B kinase/nuclear factor &kgr;B (NF-&kgr;B) pathway. Furthermore, the ability of PINK1 to promote parkin phosphorylation and activate parkin-mediated ubiquitin signaling is impaired by PD-linked pathogenic PINK1 mutations. Our findings support a direct link between PINK1-mediated phosphorylation and parkin-mediated ubiquitin signaling and implicate the deregulation of the PINK1/parkin/NF-&kgr;B neuroprotective signaling pathway in the pathogenesis of PD.</p></abstract></article-meta></front></article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo><title>Phosphorylation of parkin by Parkinson disease-linked kinase PINK1 activates parkin E3 ligase function and NF-B signaling</title></titleInfo><titleInfo type="alternative" contentType="CDATA"><title>Phosphorylation of parkin by Parkinson disease-linked kinase PINK1 activates parkin E3 ligase function and NF-B signaling</title></titleInfo><name type="personal"><namePart type="given">Di</namePart><namePart type="family">Sha</namePart><affiliation>Department of Pharmacology and Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, GA 30322, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Lih-Shen</namePart><namePart type="family">Chin</namePart><affiliation>E-mail: chinl@pharm.emory.edu</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Lian</namePart><namePart type="family">Li</namePart><affiliation>E-mail: chinl@pharm.emory.edu</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="research-article"></genre><originInfo><publisher>Oxford University Press</publisher><dateIssued encoding="w3cdtf">2010-01-15</dateIssued><dateCreated encoding="w3cdtf">2009-11-11</dateCreated><copyrightDate encoding="w3cdtf">2010</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType></physicalDescription><abstract>Mutations in PTEN-induced putative kinase 1 (PINK1) or parkin cause autosomal recessive forms of Parkinson disease (PD), but how these mutations trigger neurodegeneration is poorly understood and the exact functional relationship between PINK1 and parkin remains unclear. Here, we report that PINK1 regulates the E3 ubiquitin-protein ligase function of parkin through direct phosphorylation. We find that phosphorylation of parkin by PINK1 activates parkin E3 ligase function for catalyzing K63-linked polyubiquitination and enhances parkin-mediated ubiquitin signaling through the IB kinase/nuclear factor B (NF-B) pathway. Furthermore, the ability of PINK1 to promote parkin phosphorylation and activate parkin-mediated ubiquitin signaling is impaired by PD-linked pathogenic PINK1 mutations. Our findings support a direct link between PINK1-mediated phosphorylation and parkin-mediated ubiquitin signaling and implicate the deregulation of the PINK1/parkin/NF-B neuroprotective signaling pathway in the pathogenesis of PD.</abstract><relatedItem type="host"><titleInfo><title>Human Molecular Genetics</title></titleInfo><genre type="Journal">journal</genre><identifier type="ISSN">0964-6906</identifier><identifier type="eISSN">1460-2083</identifier><identifier type="PublisherID">hmg</identifier><identifier type="PublisherID-hwp">hmg</identifier><part><date>2010</date><detail type="volume"><caption>vol.</caption><number>19</number></detail><detail type="issue"><caption>no.</caption><number>2</number></detail><extent unit="pages"><start>352</start><end>363</end></extent></part></relatedItem><identifier type="istex">BBE18E16E039361A51A15C00DB20B747444E29B7</identifier><identifier type="DOI">10.1093/hmg/ddp501</identifier><identifier type="ArticleID">ddp501</identifier><accessCondition type="use and reproduction" contentType="copyright">The Author 2009. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissionsoxfordjournals.org</accessCondition><recordInfo><recordContentSource>OUP</recordContentSource></recordInfo></mods></metadata><covers><json:item><original>true</original><mimetype>image/tiff</mimetype><extension>tiff</extension><uri>https://api.istex.fr/document/BBE18E16E039361A51A15C00DB20B747444E29B7/covers/tiff</uri></json:item><json:item><original>true</original><mimetype>text/html</mimetype><extension>html</extension><uri>https://api.istex.fr/document/BBE18E16E039361A51A15C00DB20B747444E29B7/covers/html</uri></json:item></covers><annexes><json:item><original>true</original><mimetype>image/jpeg</mimetype><extension>jpeg</extension><uri>https://api.istex.fr/document/BBE18E16E039361A51A15C00DB20B747444E29B7/annexes/jpeg</uri></json:item><json:item><original>true</original><mimetype>image/gif</mimetype><extension>gif</extension><uri>https://api.istex.fr/document/BBE18E16E039361A51A15C00DB20B747444E29B7/annexes/gif</uri></json:item></annexes><enrichments><istex:catWosTEI uri="https://api.istex.fr/document/BBE18E16E039361A51A15C00DB20B747444E29B7/enrichments/catWos"><teiHeader><profileDesc><textClass><classCode scheme="WOS">BIOCHEMISTRY & MOLECULAR BIOLOGY</classCode><classCode scheme="WOS">GENETICS & HEREDITY</classCode></textClass></profileDesc></teiHeader></istex:catWosTEI></enrichments><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/ParkinsonV1/Data/Main/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001D63 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Corpus/biblio.hfd -nk 001D63 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Sante
|area= ParkinsonV1
|flux= Main
|étape= Corpus
|type= RBID
|clé= ISTEX:BBE18E16E039361A51A15C00DB20B747444E29B7
|texte= Phosphorylation of parkin by Parkinson disease-linked kinase PINK1 activates parkin E3 ligase function and NF-B signaling
}}
| This area was generated with Dilib version V0.6.23. |  |